Novel Zn(SO2R)2 Salts: Radical-Based Approaches to Functionalized Heteroarenes

新型 Zn(SO2R)2 盐：基于自由基的功能化杂芳烃方法

• 批准号: 8642534
• 负责人: Sarah Elizabeth Wengryniuk
• 金额: $ 4.17万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2014-12-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8642534
• 关键词: Adverse effects; Alkylation; Area; Attenuated; Biological; Carbon; Cellular Assay; Chemistry; Communities; Complex; Development; Drug Kinetics; Dyes; Electronics; Evaluation; Generations; Goals; Hand; Human body; Hydrogen Bonding; Laboratories; Lead; Libraries; Life; Mediating; Medical; Methodology; Methods; Molecular; Mono-S; Nature; Organism; Parents; Pesticides; Pharmaceutical Chemistry; Pharmaceutical Preparations; Pharmacologic Substance; Polymers; Property; Reagent; Research; Salts; Site; Societies; Vertebral column; Vitamins; Zinc; alkyl group; appendage; base; biological systems; design; functional group; improved; interest; novel; programs; scaffold; screening; success; tool

DESCRIPTION (provided by applicant): Arenes and heteroarenes are omnipresent in both nature and society, and can be found throughout the human body and in other organisms, as well as in vitamins, drugs, dyes, pesticides, polymers and literally all other aspects of life. As these molecular frameworks form the backbones of some of the most important compounds in both biological systems and industrial applications, the need for methods for their functionalization and derivatization is of the utmost importance. Of particular interest are methods for the direct formation of carbon-carbon bonds through the introduction of alkyl and fluorinated alkyl groups. Alkyl groups serve medicinal chemists by improving pharmacokinetic profiles as well as providing functional handles, and fluoroalkyl appendages are widely utilized as they can serve as attenuated bioisoteres of more reactive and labile functionalities. The proposed research aims to expand upon a recently developed method in our laboratory for the direct, site-selective incorporation of alkyl and fluoroalkyl motifs into heteroarenes. Building on initial proof of concept studies, a "tool kit" of reagents will be synthesized and screened for ther ability to functionalize simple heteroarenes. Once synthesized, a method for sequential addition of multiple groups in a one-pot, site-selective fashion will be developed, taking advantage of the inherent nucleophilic or electrophilic character of each alkyl radical species. Finally, the long-term goal for this research is the application of this novel methodology to complex heteroarene backbones of biologically relevant compounds. Success in these goals would have an immediate impact on the medical community, giving medicinal chemists a new avenue for the rapid generation of interesting and diverse lead compounds for biological evaluation.

描述（由申请人提供）：竞技场和杂产在自然和社会中都是无所不在的，可以在整个人体，其他生物以及维生素，药物，染料，农药，聚合物以及实际上其他所有方面都可以找到。由于这些分子框架构成了生物系统和工业应用中一些最重要化合物的骨干，因此对它们的功能化和衍生化方法的需求至关重要。特别有趣的是通过引入烷基和氟化烷基直接形成碳碳键的方法。烷基通过改善药代动力学特征和提供功能手柄来服务药物学家，并且氟烷基附属物被广泛使用，因为它们可以用作减弱的生物发病因子，具有更具反应性和不稳定功能的生物发散性。拟议的研究旨在扩展我们的实验室中最近开发的方法，即将烷基和氟烷基基序的直接现场选择性掺入到杂种中。建立 概念研究的最初证明，将合成和筛选一种试剂的“工具套件”，以使其功能化简单杂种烯。一旦合成，将开发一种在单盘，现场选择性方式中顺序添加多组的方法，利用每个烷基自由基物种的固有亲核或亲电性特征。最后，这项研究的长期目标是将这种新方法应用于生物学相关化合物的复杂杂种骨架上。这些目标的成功将对医学界产生直接的影响，为药物化学家提供新的途径，以快速产生有趣而多样化的铅化合物进行生物学评估。

项目成果

Regioselective bromination of fused heterocyclic N-oxides.

• DOI: 10.1021/ol3034675
• 发表时间: 2013-01
• 期刊: Organic letters
• 影响因子: 5.2
• 作者: Sarah E. Wengryniuk;A. Weickgenannt;Christopher A. Reiher;N. Strotman;K. Chen;Martin D. Eastgate;P. Baran